Centre for Craniofacial and Regenerative Biology, Department of Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, UK.
Institute of Animal Physiology and Genetics, Czech Academy of Sciences, 602 00 Brno, Czech Republic.
Development. 2019 Feb 8;146(3):dev171363. doi: 10.1242/dev.171363.
Most mammals have two sets of teeth (diphyodont) - a deciduous dentition replaced by a permanent dentition; however, the mouse possesses only one tooth generation (monophyodont). In diphyodonts, the replacement tooth forms on the lingual side of the first tooth from the successional dental lamina. This lamina expresses the stem/progenitor marker Sox2 and has activated Wnt/β-catenin signalling at its tip. Although the mouse does not replace its teeth, a transient rudimentary successional dental lamina (RSDL) still forms during development. The mouse RSDL houses Sox2-positive cells, but no Wnt/β-catenin signalling. Here, we show that stabilising Wnt/β-catenin signalling in the RSDL in the mouse leads to proliferation of the RSDL and formation of lingually positioned teeth. Although Sox2 has been shown to repress Wnt activity, overexpression of Wnts leads to a downregulation of Sox2, suggesting a negative-feedback loop in the tooth. In the mouse, the first tooth represses the formation of the replacement, and isolation of the RSDL is sufficient to induce formation of a new tooth germ. Our data highlight key mechanisms that may have influenced the evolution of replacement teeth.This article has an associated 'The people behind the papers' interview.
大多数哺乳动物有两套牙齿（双牙列）——乳牙被恒牙替换；然而，老鼠只有一代牙齿（单牙列）。在双牙列动物中，替换牙从连续的牙蕾的舌侧形成。该牙蕾表达干细胞/祖细胞标志物 Sox2，并在其顶端激活 Wnt/β-catenin 信号。尽管老鼠不更换牙齿，但在发育过程中仍然会形成短暂的、原始的后继牙蕾（RSDL）。鼠 RSDL 中含有 Sox2 阳性细胞，但没有 Wnt/β-catenin 信号。在这里，我们表明在鼠的 RSDL 中稳定 Wnt/β-catenin 信号会导致 RSDL 的增殖和舌侧定位牙齿的形成。尽管 Sox2 被证明可以抑制 Wnt 活性，但 Wnt 的过表达会导致 Sox2 的下调，这表明牙齿中存在负反馈环。在老鼠中，第一颗牙齿抑制了替换牙的形成，而 RSDL 的隔离足以诱导新的牙原基的形成。我们的数据强调了可能影响替换牙进化的关键机制。本文有一个相关的“论文背后的人物”采访。
